Significant advances have been made in the design and synthesis of nonpeptidal ligands for the HIV protease substrate binding site. See, S. Thaisrivong, Annual Reports on Med. Chem., 29, p. 133 (1994). The structure-based design of bis-tetrahydrofuran ligands that can effectively replace two amide bonds and a 10n-aromatic system of an HIV protease inhibitor has been reported (A. K. Ghosh et al., J. Med. Chem., 37, p. 2506 (1994)).
The present commercial method of synthesizing the compound of structural formula (I) provides a racemic mixture, which requires enzymatic resolution to provide optically active ligands with high enantiomeric excess. The preparation of a racemic mixture, and subsequent resolution to provide compound (I), significantly reduces the yield of the desired enantiomer because about one-half of the racemic mixture, i.e., the undesired enantiomer, is wasted. In addition, costs are increased because about one-half of the starting materials and reagents used in the synthesis are wasted.
In particular, the following synthetic scheme (1) illustrates the present commercial method of synthesizing compound (I). This synthesis is disclosed in detail in A. K. Ghosh et al., Tetrahedron Letters, 36(4), pp. 505-508 (1995), incorporated herein by reference. Also see, A. K. Ghosh et al., J. Med. Chem., 39, pp. 3278-3290 (1996) for the synthesis of compound (I) and a related compound of structural formula (II) (i.e., (3S,3aR,7aS)-3-hydroxyhexahydrofuro[2,3-b]pyran). 
There is a need in the art to provide an improved method of synthesizing compound (I), stereoisomers of (I), and related compounds, like compound (II). In particular, a need exists for a short synthetic route that avoids generation of a racemic mixture, and, therefore, increases yield of the desired enantiomer and decreases costs.
There also is a need in the art for an improved synthesis of precursors to compound (I), for example (5S)-5-(benzyloxymethyl)-5H-furan-2-one.